Abstract 121P
Background
The treatment with immune checkpoint inhibitors (ICIs) is the gold standard therapy in MSI/dMMR mCRC patients. However, 15-30% of MSI mCRC achieve progression disease (PD) as best response (BR). The development of predictive biomarkers of primary resistance to ICIs could assist the choice of the best treatment. The aim of this preliminary analysis was to confirm the predictive value of early and easy-to-retrieve biomarkers of response to ICIs in MSI mCRC.
Methods
We retrospectively collected data of pts with unresectable MSI mCRC treated with immunotherapy at Vall d’Hebron Hospital from 2015 to 2023. Neutrophil to lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) were computed as the early change between baseline and after 6-8 weeks of treatment. The endpoints assessed included BR, progression-free survival at 12 months (12mPFS), and progression-free survival (PFS). To identify biomarkers associated with BR and 12mPFS, a univariable logistic regression model was employed, while biomarkers associated with PFS were analyzed using a univariable Cox proportional hazards model and Kaplan-Meier curves. PIV and CEA cut-offs were determined using the maximally selected logrank statistics in the PFS and NLR cut-off was established at 3, as in previous reports.
Results
In this preliminary analysis, 61 consecutive pts with data avaiable were included. We confirmed the predictive value of NLR and PIV in terms of BR to ICIs, as both NLR > 3 (p = .049) and PIV > 408 (p =.029) were significantly associated with PD as BR. High PIV (p = .001), but not NLR, was also correlated with PFS < 12 months. Early increase of at least 30% of PIV (p 0.07) but not of NLR, had a tendency to associate with PD as BR. CEA > 13.1 ng/ml had a tendency to associate with longer PFS (p=.053). Baseline tumor burden and number of metastatic sites were not predictive of PFS.
Conclusions
Our preliminary data confirm that high NLR and PIV predict primary resistance to immunotherapy, with PIV also associated with duration of benefit. Besides, baseline tumor size and number of metastatic sites are not informative of ICIs benefit. Association of higher CEA and longer PFS deserves further analyses.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Travel and accommodation expenses and Speaker: Amgen, Merck; Other, Travel and accommodation expenses: Pierre Fabre, Sanofi. F. Salvà Ballabrera: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi, Merck, Servier, Roche, Terumo Company. I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Accommodation and travel expenses: Amgen, Merck, Sanofi, Servier. N. Saoudi Gonzalez: Financial Interests, Personal, Invited Speaker: Amgen; Other, Travel: Amgen, Merck. M. Rodriguez Castells: Financial Interests, Personal, Invited Speaker: Rovi; Other, Travel and accommodation: BMS, Merck; Other, Travel and Accommodation: Amgen. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics, CARSgen Therapeutics, hC Bioscience Inc, Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc, Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd., Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGaA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune, AbbVie Deutschland GmbH & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., BioNTech Rna Pharmaceuticals GmbH, BioNTech Small Molecules GmbH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, accommodation, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. All other authors have declared no conflicts of interest.